crossing96/oncoscreening huggingface dataset:
Use of thiazolidinediones and risk of bladder cancer: disease or drugs?	BACKGROUND: Pioglitazone, a drug for the treatment of type 2 diabetes mellitus has been associated with bladder cancer in observational studies. Diabetes mellitus itself has also been linked with bladder cancer. The objective was to estimate the risk of bladder cancer for diabetic patients using thialozidinediones (TZDs) compared with patients in other treatment stages of the disease. METHODS: We performed a population-based cohort study (1996-2007) in the Danish National Health Registers. Oral antidiabetic drug users (n=179,056) were matched 1:3 by sex and year of birth to non-users. Hazard ratios (HRs) of bladder cancer were estimated using Cox proportional hazards models. Time-dependent adjustments were made for age, comorbidity, and drug use. Four different treatment stages were defined: current use of either a biguanide or a sulfonylureum (stage 1), current use of a biguanide and a sulfonylureum at the same time (stage 2), current use of TZDs (stage 3) and current use of insulin (stage 4). RESULTS: Compared with non-diabetic controls, patients using antidiabetic medication experienced a 1.3-fold increased risk of bladder cancer (adjusted HR 1.3 [95%CI 1.2-1.4]). No major differences were observed between the different treatment stages. The risk of bladder cancer varied between 1.2 [95%CI 1.0-1.4] in stage 4 and 1.4 [95%CI 1.3-1.6] in stage 1. The risk of bladder cancer with TZD use (stage 3) was similar to the other groups (adjusted HR 1.3 [95%CI 0.6-2.7]). INTERPRETATION: The association between TZD use and bladder cancer is probably confounded by the underlying disease.	bladder
Prognostic role of survivin in bladder cancer: a systematic review and meta-analysis.	PURPOSE: The objective of the present study was to conduct a systematic review and meta-analysis of published literature investigating the survivin expression and its effects on bladder cancer prognosis. MATERIALS AND METHODS: We carefully searched online Pubmed, Cochrane Library and SCOPUS database from August 1997 to May 2013. RESULTS: A total of 14 articles met the eligibility criteria for this systematic review. The eligible studies included a total of 2,165 patients with a median number of 155 patients per study (range: 17-726). Of the 14 studies, nine evaluated immunohistochemistry in formalin-fixed paraffin-embedded tissue blocks. In non-muscle invasive bladder tumor, the pooled hazard ratio (HR) was statistically significant for recurrence-free survival (pooled HR, 1.81; 95% confidence interval [CI], 1.30-2.52), progression-free survival (pooled HR, 2.12; 95% CI, 1.60-2.82), cancer-specific survival (pooled HR, 2.01; 95% CI, 1.32-3.06), and overall survival (pooled HR, 1.53; 95% CI, 1.02-2.29). The overall HRs by survivin status were robust across advanced stages. When only adjusted survival data were included, statistically significant differences were identified for all survival subgroup analyses. There was no between-study heterogeneity in the effect of survivin status on the majority of meta-analyses. There was no clear evidence of publication bias in this meta-analysis. CONCLUSIONS: Survivin expression indicates worse prognosis in patients with bladder cancer but the results should be interpreted with caution. It is necessary that better-designed studies with standardized assays need to provide a better conclusion about the relationship between survivin expression and the outcome of patients with bladder cancer.	bladder
[Paraneoplastic cerebellar degeneration with bladder cancer confirmed the existence of an anti-neural antibody: a case report].	A 66-year-old man was diagnosed with bladder cancer at our urology department. Three months later, he developed subacute progressive cerebellar limb ataxia and truncal oscillation. Analysis of cerebrospinal fluid showed pleocytosis and increased concentrations of protein, while brain magnetic resonance imaging revealed no abnormalities. Based on the presence of the bladder cancer, the etiology of subacute cerebellar ataxia could be a paraneoplastic neurological syndrome. Four months later, the patient underwent transurethral resection of the bladder tumor, which was identified as urothelial cancer on the basis of pathological examinations. However, this procedure failed to improve his neurological symptoms. Serum paraneoplastic markers such as anti-Yo, anti-Hu, anti-Tr, and other antibodies were not detected. Immunohistochemical staining of mouse cerebellum using the patient's serum revealed coarse granular staining in the cytoplasm of Purkinje cells and diffuse staining in the neuropil of the molecular layer, suggesting the presence of an unknown antibody. Subsequently, one-dimensional electrophoresis western blotting using the patient's serum revealed several bands including a strong positive band of approximately 45 kDa in mouse cerebellum lysates but not in liver lysates. These bands have never been detected in sera derived from healthy donors. These results suggested the presence of a novel antibody in the patient's serum that might recognize the approximately 45 kDa protein related to paraneoplastic cerebellar degeneration. Cases of paraneoplastic neurological syndrome associated with bladder cancer have rarely been reported. We concluded that the present case may be categorized as paraneoplastic neurological syndrome caused by an unknown antibody.	bladder
Detection of specific chromosomal aberrations in urine using BCA-1 (oligo-CGH-array) enhances diagnostic sensitivity and predicts the aggressiveness of non-muscle-invasive bladder transitional cell carcinoma.	INTRODUCTION: Bladder carcinoma (B-TCC) is the fifth most prevalent carcinoma in the United States (US) or Europe. In addition, B-TCC is the most expensive carcinoma per patient between diagnosis and death, because of its 50-80 % recurrence rate. B-TCC is an optimal carcinoma for which to detect DNA alterations in urine, which is easily obtainable. Chromosomal aberrations in tumors have been closely related to the carcinogenesis process. MATERIAL AND METHODS: We developed a highly specific and sensitive oligo-CGH-array for the diagnosis and follow-up of B-TCC, based on the detection of chromosomal aberrations in urine samples. One hundred and sixty-four urine samples were analyzed. The qualitative results, including chromosomal aberrations, were obtained. Quantitative results are expressed as a percentage of chromosomal alterations on the autosomes. RESULTS: From the urine samples, we were able to differentiate B-TCC from non-malignant conditions with an accuracy of 100 % for patients without history of B-TCC. For follow-up of B-TCC in clinical practice, at least a deletion (8p; 9p; 9q) or a cut-off of >2 % of chromosomal imbalance was considered as a positive test. According to our criteria, 100 % of high-grade tumors were diagnosed, and the sensitivity to predict positive cystoscopy was 95 % (specificity 73 %). A cut-off >9 % was a strong signature of high-grade TCC (odds ratio 53 CI 95 % 7-417; p = 0.0002). CONCLUSION: We developed a sensitive clinical tool for the detection of B-TCC using DNA extracted from patient urine. This tool is also able to identify low-grade B-TCC and identify high-risk patients harboring a high-grade disease.	bladder
Frozen section analysis of ureteral margins in patients undergoing radical cystectomy for bladder cancer: differential impact of carcinoma in situ in the bladder on reliability and impact on tumour recurrence in the upper urinary tract.	BACKGROUND: Patients undergoing radical cystectomy (RC) for urothelial carcinoma of the bladder (UCB) are at risk for upper urinary tract recurrence (UUTR), especially in case of carcinoma in situ (CIS). Data on the impact of CIS in the urinary bladder on ureteral tumour involvement or UUTR are conflicting. We presently evaluate the accuracy of intraoperative frozen section analysis (FSA) of the ureteral margin, the incidence of ureteral tumour involvement and their impact on UUTR in patients undergoing RC for UCB with versus without CIS of the bladder. MATERIAL AND METHODS: Between 2003 and 2007, 243 patients underwent RC in our department. 176 of these for UCB, either without CIS (n = 117, group I) or solitary/concomitant CIS (n = 59, group II). FSA was performed. Patients were followed up for UUTR. RESULTS: Overall, 403 ureteral margins--including re-resections--were analysed (group I, n = 232; group II, n = 171). One patient (0.85%) in group I and 21 patients (35.6%) in group II had tumour involvement of the ureter (p < 0.0001) at the time of RC. The false-negative rate of FSA compared to final histopathology was 0.4% (1/232) for group I and 2.9% (5/171) for group II, respectively. Mean duration of follow-up was 26 months (1-72). In group II, 2 patients (1.1%) had UUTR in the follow-up; both had initially positive and subsequently false-negative FSA. CONCLUSIONS: Tumour involvement of the ureter is found significantly more often in solitary or concomitant CIS of the bladder. Intraoperative ureteral FSA is accurate and should be recommended in these patients. Ureteral tumour involvement predisposes to UUTR especially with initial positive margins mandating careful follow-up.	bladder
A modified method for isolation of bladder cancer stem cells from a MB49 murine cell line.	BACKGROUND: The vaccine was efficiently effective against bladder cancer in earlier studies. However, a part of the mouse bladder tumour regrew due to regression after a period of time as the cancer stem cells could not be eliminated. In this study, we showed a modified method for the isolation of MB49 bladder cancer stem cells (MCSCs). METHODS: Through a comparison of different serum-free culture mediums (SFM), MCSCs were isolated by a combination of the limited dilution method and the optimal SFM method. The characterizations of MCSCs were verified by the fluorescence activated cell sorting, the quantitative polymerase chain reaction, the western blotting, the cell proliferation assay, the soft agar assay, the transwell assay, the resistance to chemotherapy assay and the tumor xenograft formation assay. RESULTS: The optimal SFM contained a RPMI1640+ epidermal growth factor (20 ng/ml), a basic fibroblast growth factor (20 ng/ml), a leukemia inhibitory factor (20 ng/ml), a B-27 serum-free supplement (20 μl/ml), and a bovine serum albumin (4 μg/ml). MCSCs possessed the high expression of cancer stem cell markers (CD133, CD44, OCT4, NANOG, and ABCG2) and the ability of differentiation. In functional comparisons, MCSCs had higher proliferative abilities, lower susceptibility to chemotherapy, greater migration in vitro, and stronger tumorigenic abilities in vivo. CONCLUSION: MCSCs displayed specific cancer stem cells properties. Our study showed MCSCs were isolated successfully with a modified method using a combination of limited dilution and SFM methods.	bladder
MicroRNA-124-3p inhibits cell migration and invasion in bladder cancer cells by targeting ROCK1.	BACKGROUND: Increasing evidence has suggested that dysregulation of certain microRNAs (miRNAs) may contribute to human disease including carcinogenesis and tumor metastasis in human. miR-124-3p is down-regulated in various cancers, and modulates proliferation and aggressiveness of cancer cells. However, the roles of miR-124-3p in human bladder cancer are elusive. Thus, this study was conducted to investigate the biological functions and its molecular mechanisms of miR-124-3p in human bladder cancer cell lines, discussing whether it has a potential to be a therapeutic biomarker of bladder cancer. METHODS: Three human bladder cancer cell lines and samples from ten patients with bladder cancer were analyzed for the expression of miR-124-3p by quantitative RT--PCR. Exogenetic overexpression of miR-124-3p was established by transfecting mimics into T24, UM-UC-3 and J82 cells, after that cell proliferation and cell cycle were assessed by MTT assay, flow cytometry and Colony-forming assay. Cell motility and invasion ability were evaluated by wound healing assay and transwell assay. Tissue microarray, and immunohistochemistry with antibodies against ROCK1, MMP2 and MMP9 was performed using the peroxidase and DAB methods. The target gene of miR-124-3p was determined by luciferase assays, quantitative RT--PCR and western blot. The regulation of epithelial-to-mesenchymal transition by miR-124-3p was analyzed by western blot. RESULTS: miR-124-3p is frequently down-regulated in bladder cancer both in three bladder cancer cell lines, T24, UM-UC-3, J82 and clinical samples. Overexpression of miR-124-3p induced G1-phase arrest in T24, UM-UC-3 and J82 cell lines and suppressed cell growth in colony-forming assay. miR-124-3p significantly repressed the capability of migration and invasion of bladder cancer cells. In addition, ROCK1 was identified as a new target of miR-124-3p. ROCK1, MMP2, MMP9 were up-regulated in bladder cancer tissues. Furthermore, we demonstrated miR-124-3p could inhibit bladder cancer cell epithelial mesenchymal transfer, and regulated the expression of c-Met, MMP2, MMP9. CONCLUSIONS: miR-124-3p can repress the migration and invasion of bladder cancer cells via regulating ROCK1. Our data indicate that miR-124-3p could be a tumor suppressor and may have a potential to be a diagnostics or predictive biomarker in bladder cancer.	bladder
[Transurethral bladder resection of non muscle invasive bladder cancer with Hexvix ®].	Bladder neoplasms are the second most frequent urological cancer after prostate cancer. Bladder neoplasms arise from urothelial tissue and can either be restricted within the Mucosa and the Lamina Propria (i.e., non muscle invasive bladder cancer [NMIBC]) or invade the Muscularis Propria (i.e., muscle invasive bladder cancer [MIBC]). An exhaustive transuretral resection of the bladder tumor (TURBT) has always been seen a surrogate of quality for the initial step of the treatment. Although a large majority of bladder tumors can be easily identified macroscopically, there are flat lesions (i.e., carcinoma in situ [CIS]), which are more difficult to diagnose. To improve detection of flat lesions, a fluorescence diagnosis under blue light has been proposed during cystoscopy. Photodynamic diagnosis is performed using blue light after preoperative intravesical instillation of hexaminolaevulinic acid (Hexvix(®)) to enhance visual contrast between urothelial cancer and normal tissue. Thus, the quality of TURBT appears to be improved in selected cases with a controversial benefit on the recurrence free survival. Due to its medico-economical constraints, worldwide spread of fluorescence cystoscopy is still limited and restricted to specific cases.	bladder
Clinicopathological characteristics of incidental prostate cancer discovered from radical cystoprostatectomy specimen: a multicenter French study.	PURPOSE: The present study assessed the incidence and histopathological features of incidentally diagnosed prostate cancer (PCa) in specimens from radical cystoprostatectomy (RCP) for bladder cancer. The patient outcomes also were evaluated. METHODS: We retrospectively reviewed the histopathological features and survival data of 4,299 male patients who underwent a RCP for bladder cancer at 25 French centers between January 1996 and June 2012. No patients had preoperative clinical or biological suspicion of PCa. RESULTS: Among the 4,299 RCP specimens, PCa was diagnosed in 931 patients (21.7%). Most tumors (90.1%) were organ-confined (pT2), whereas 9.9% of them were diagnosed at a locally advanced stage (≥pT3). Gleason score was <6 in 129 cases (13.9%), 6 in 575 cases (61.7%), 7 (3 + 4) in 149 cases (16.0%), 7 (4 + 3) in 38 cases (4.1%), and >7 in 40 cases (4.3%). After a median follow-up of 25.5 months (interquartile range 14.2-47.4), 35.4% of patients had bladder cancer recurrence and 23.8% died of bladder cancer. Only 16 patients (1.9%) experienced PCa biochemical recurrence during follow-up, and no preoperative predictive factor was identified. No patients died from PCa. CONCLUSIONS: The rate of incidentally diagnosed PCa in RCP specimens was 21.7%. The majority of these PCas were organ-confined. PCa recurrence occurred in only 1.9% of cases during follow-up.	bladder
Small cell carcinoma of the urinary bladder: a contemporary review with a special focus on bladder-sparing treatments.	Small cell carcinoma of the urinary bladder (SCCUB) is a rare and aggressive disease. To date, no standard treatment has been proposed due to the lack of prospective studies resulting from the rarity of this disease. Recently published studies of relatively large patient cohorts, however, have shed some light on the management of SCCUB patients. In this article, the authors review the epidemiology, pathogenesis, diagnosis and treatment (based on disease stage), and they then discuss the optimal therapeutic strategy for SCCUB patients, particularly for those with limited, locoregional disease. The authors conclude that multidisciplinary approaches are needed for the optimal management of this aggressive disease. The authors also discuss bladder-sparing approaches for SCCUB patients, compared to those for conventional bladder urothelial carcinoma patients.	bladder
Evaluation of the antitumor activity of dacomitinib in models of human bladder cancer.	Members of the human epidermal growth factor receptor (HER) family play a significant role in bladder cancer progression and may underlie the development of chemotherapy resistance. Dacomitinib is an irreversible tyrosine kinase inhibitor with structural specificity for the catalytic domains of epidermal growth factor receptor (EGFR), HER2 and HER4 that has exhibited vigorous efficacy against other solid tumors. We evaluated the antitumor activity of dacomitinib in human bladder cancer cell lines expressing varying levels of HER family receptors. These cell lines also were established as bladder cancer xenografts in nonobese diabetic/severe combined immunodeficiency (NOD/SCID) mice to assess dacomitinib activity in vivo. Significant cytotoxic and cytostatic effects were noted in cells expressing elevated levels of the dacomitinib target receptors with apoptosis and cell cycle arrest being the predominant mechanisms of antitumor activity. Cells expressing lower levels of HER receptors were much less sensitive to dacomitinib. Interestingly, dacomitinib was more active than either trastuzumab or cetuximab in vitro, and exhibited increased growth inhibition of bladder tumor xenografts compared with lapatinib. Pharmacodynamic effects of dacomitinib included decreased E-cadherin (E-cad) expression, reduction of EGFR and extracellular signal-regulated kinase (ERK) phosphorylation and reduced mitotic count. Dacomitinib also inhibited tumor growth in a chemotherapy-resistant xenograft and, when combined with chemotherapy in a sensitive xenograft, exhibited superior antitumor effects compared with individual treatments. Evaluation in xenograft-bearing mice revealed that this combination was broadly feasible and well tolerated. In conclusion, dacomitinib exhibited pronounced activity both as a single agent and when combined with chemotherapy in human bladder cancer models. Further investigation of dacomitinib in the preclinical and clinical trial settings is being pursued.	bladder
The role of urine markers, white light cystoscopy and fluorescence cystoscopy in recurrence, progression and follow-up of non-muscle invasive bladder cancer.	Non-muscle invasive bladder cancer (NMIBC) accounts for approximately 70 % of all bladder cancer cases and represents a heterogeneous pathological entity, characterized by a variable natural history and oncological outcome. The combination of cystoscopy and urine cytology is considered the gold standard in the initial diagnosis of bladder cancer, despite the limited sensitivity. The first step in NMIBC management is transurethral resection of the bladder tumour (TURBT). This procedure is marked by a significant risk of leaving residual disease. The primary landmark in NMIBC is the high recurrence rate. Fluorescence cystoscopy improves the bladder cancer detection rate, especially for flat lesions, and improves the recurrence-free survival by decreasing residual tumour. Progression to muscle invasive tumours constitutes the second important landmark in NMIBC evolution. Stage, grade, associated CIS and female gender are the major prognostic factors in this regard. The evolution to MIBC has a major negative impact upon the survival rate and quality of life of these patients. Fluorescence cystoscopy improves the detection rate of bladder cancer but does not improve the progression-free survival. Urine markers such as ImmunoCyt and Uro Vysion (FISH) have also limited additional value in diagnosis and prognosis of NMIBC patients. Major drawbacks are the requirement of a specialized laboratory and the additional costs. In this review, the risks of recurrence and progression are analysed and discussed. The impact of white light cystoscopy, fluorescence cystoscopy and urine markers is reviewed. Finally, the means and recommendations regarding follow-up are discussed.	bladder
What about conventional laparoscopic radical cystectomy? Cost-analysis of open versus laparoscopic radical cystectomy.	PURPOSE: To assess direct healthcare costs for open radical cystectomy (ORC) vs laparoscopic radical cystectomy (LRC) with ileal conduit. PATIENTS AND METHODS: A series of 44 and 42 patients undergoing ORC and LRC with ileal conduit were retrospectively analyzed at a single institution from January 2005 to January 2012. The ORC and LRC procedures were performed by two independent surgical teams; there was no selection in patients. Data on patient demographics, perioperative outcome parameters, complications, and readmissions were gathered retrospectively in the ORC series and prospectively in the LRC series. Direct healthcare costs were evaluated for operating room occupation, disposable surgical equipment, blood transfusions, hospital stay according to intensity of care, and readmission days. RESULTS: Mean and median evaluated total direct healthcare costs per patient did not differ significantly and were 17,534€ and 16,511€ in the LRC group and 22,284€ and 15,909€ in the ORC group. Excess costs for disposable surgical equipment and operating room occupation within the LRC group were compensated for as a result of shorter hospital stay, lower number of blood transfusions, and intensive-care admissions. Minor and major complication rates were comparable between groups. CONCLUSION: Within our series, LRC is a cost neutral minimally invasive alternative to ORC without comprising quality of care and with beneficial perioperative outcomes.	bladder